Impairment of the immune system has been suggested to be responsible for smoke-associated respiratory tract infections, chronic bronchitis and neoplasia. Therefore, understanding how smoking may alter the immune system is of primary concern in these disorders. The experiments outlined in this proposal are directed to determine how cigarette smoke may affect the immunological response of the lung, which may determine its susceptibility to pathogens and neoplasia. The overall objective is to understand the manner in which inhalation of cigarette smoke affects the immune response. The rat has been chosen as the test species in the initial experiments because of its frequent use as an experimental animal in studies related to tobacco smoke toxicity and because it has been demonstrated to undergo histopathological changes in the lung upon chronic inhalation of cigarette smoke. Preliminary results have demonstrated that chronic inhalation of cigarette smoke severely and preferentially inhibited the antibody response of lung-associated lymph nodes (LAL). Moreover, since the response to T cell mitogens in the same LAL cells was not significantly altered, the inhibition of the antibody response did not appear to be mediated by non-specific factors. Experiments have been proposed to ascertain the cellular basis of smoke-induced immunosuppression. The studies will examine whether chronic smoke inhalation laters the migration or retention of antigens in LAL tissues, and/or the functional activities of T cells, B cells or macrophages. The assays to test these parameters will include primary and secondary antibody responses, in vitro allograft reactivity, antigen-dependent proliferation and fractionation protocols using panning or fluorescence-activated cell sorting to isolate specific cell populations. We will also attempt to define the components of cigarette smoke that may be responsible for the smoke-induced effects on the immune system. Experiments have also been suggested to investigate whether the immune system returns to normal after inhalation of cigarette smoke is stopped, and whether passive smoking also impairs the immune system.